Over the past several years, the medical community has learned, to its dismay, that we can experience a “twin-demic” of winter infectious diseases – simultaneous COVID-19 and flu outbreaks resulting in intense stresses on healthcare delivery. Broad uptake of COVID and flu vaccines can alleviate those stresses somewhat, but, despite the proven safety and efficacy of the vaccines, there remain some difficult, unresolved questions.
One is whether there is an advantage — or perhaps a disadvantage — to getting COVID and flu shots at the same time, as is often recommended. A recent study published in the medical journal The Lancet Regional Health addressed that question. The somewhat equivocal conclusions create a dilemma for individuals, public health officials, and practicing physicians. Let me explain.
The “Timing and sequence of vaccination against COVID-19 and influenza” (TACTIC) study looked at the effects of various vaccination regimens on seniors. It enrolled 154 fully COVID-vaccinated individuals over 60 into a single-blind, placebo-controlled, randomized clinical trial and administered different COVID-19/flu booster regimens."
There were four groups: (1) Pfizer COVID booster (bivalent Omicron BA.1–adapted) first and quadrivalent flu vaccine three weeks later; (2) quadrivalent flu vaccine first and Pfizer COVID booster three weeks later; (3) both simultaneously; and (4) Pfizer COVID booster alone.
As an indicator of efficacy, the investigators measured blood-neutralizing antibodies against three sets of COVID virus spike proteins: the original SARS-CoV-2 spike protein, Delta, and Omicron BA.1 variants of concern.
The important finding was that administration of the COVID-19 booster and flu vaccines together compared to booster vaccination alone did not meet the pre-defined criteria for non-inferiority for the primary outcome of IgG binding against spike protein of SARS-CoV-2 and showed less potent neutralization against Delta and Omicron BA.1 variants.
That requires some unpacking. “Non-inferiority” is a somewhat ambiguous concept: In non-inferiority studies, the objective is to demonstrate that a therapy is not inferior (i.e., is equivalent or possibly superior) to another. In the TACTIC study, administering the COVID and flu vaccines together failed to show non-inferiority. The investigators’ stated their somewhat equivocal conclusions this way:
Concurrent administration of both vaccines is safe, but the quantitative and functional antibody responses were marginally lower compared to booster vaccination alone. Lower protection against COVID-19 with concurrent administration of COVID-19 and influenza vaccination cannot be excluded, although additional larger studies would be required to confirm this.
Influenza virus, courtesy of NIAID/NIH
So, where does that leave medical practitioners and public health officials? In short, in a quandary.
From the results of the TACTIC study, the most conservative and prudent approach is probably to get the flu and COVID shots at least three weeks apart to ensure maximum efficacy (as measured by antibody binding).
However, there's the "human factor" to consider. Resistance to vaccination has increased in recent years, in large part because of the vaccine misinformation and disinformation promulgated during the pandemic. There is also vaccine fatigue, defined as “unwillingness or inaction towards vaccine information or instruction due to perceived burden or burnouts.” Some of that currently is due to the succession of shots, including COVID’s first round (two shots) and subsequent boosters. (A measure of such fatigue is that only about 17% of Americans are now fully boosted.)
Thus, it seems likely that many people would be put off by the bother of getting the COVID and flu vaccines on separate occasions several weeks apart and that compliance would suffer even in people who were not opposed to the vaccines.
Especially given the equivocal results of the TACTIC study, I opt for transparency, so I recommend that physicians and other healthcare providers explain what we know and our areas of uncertainty — as I have tried to do here — and let people make their own decisions. As for me, personally, it’s easy to stop at the local pharmacy to get a shot, so I’ll probably take the conservative approach and get the vaccines on separate occasions.
An earlier version of this article was previously published by the Genetic Literacy Project.
Henry I. Miller, MS, MD
Henry I. Miller, MS, MD, is the Glenn Swogger Distinguished Fellow at the American Council on Science and Health. His research focuses on public policy toward science, technology, and medicine, encompassing a number of areas, including pharmaceutical development, genetic engineering, models for regulatory reform, precision medicine, and the emergence of new viral diseases. Dr. Miller served for fifteen years at the US Food and Drug Administration (FDA) in a number of posts, including as the founding director of the Office of Biotechnology.
